Supachai Tanomsup

Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study

BACKGROUND Obesity is a major risk factor for cardiovascular disease, but the most predictive measure for different ethnic populations is not clear. We aimed to assess whether markers of obesity, especially waist-to-hip ratio, would be stronger indicators of myocardial infarction than body-mass index (BMI), the conventional measure. METHODS We did a standardised case-control study of acute myocardial infarction with 27 098 participants in 52 countries (12,461 cases and 14,637 controls) representing several major ethnic groups. We assessed the relation between BMI, waist and hip circumferences, and waist-to-hip ratio to myocardial infarction overall and for each group. FINDINGS BMI showed a modest and graded association with myocardial infarction (OR 1.44, 95% CI 1.32-1.57 top quintile vs bottom quintile before adjustment), which was substantially reduced after adjustment for waist-to-hip ratio (1.12, 1.03-1.22), and non-significant after adjustment for other risk factors (0.98, 0.88-1.09). For waist-to-hip ratio, the odds ratios for every successive quintile were significantly greater than that of the previous one (2nd quintile: 1.15, 1.05-1.26; 3rd quintile: 1.39; 1.28-1.52; 4th quintile: 1.90, 1.74-2.07; and 5th quintiles: 2.52, 2.31-2.74 [adjusted for age, sex, region, and smoking]). Waist (adjusted OR 1.77; 1.59-1.97) and hip (0.73; 0.66-0.80) circumferences were both highly significant after adjustment for BMI (p<0.0001 top vs bottom quintiles). Waist-to-hip ratio and waist and hip circumferences were closely (p<0.0001) associated with risk of myocardial infarction even after adjustment for other risk factors (ORs for top quintile vs lowest quintiles were 1.75, 1.33, and 0.76, respectively). The population-attributable risks of myocardial infarction for increased waist-to-hip ratio in the top two quintiles was 24.3% (95% CI 22.5-26.2) compared with only 7.7% (6.0-10.0) for the top two quintiles of BMI. INTERPRETATION Waist-to-hip ratio shows a graded and highly significant association with myocardial infarction risk worldwide. Redefinition of obesity based on waist-to-hip ratio instead of BMI increases the estimate of myocardial infarction attributable to obesity in most ethnic groups.

Effect of Nesiritide in Patients with Acute Decompensated Heart Failure

BACKGROUND Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Dronedarone in high-risk permanent atrial fibrillation

BACKGROUND Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

Dabigatran Versus Warfarin Effects on Ischemic and Hemorrhagic Strokes and Bleeding in Asians and Non-Asians With Atrial Fibrillation

Background and Purpose— Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries. Methods— There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used. Results— Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3–4.7; P=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03–0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06–0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19–0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13–0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year). Conclusions— Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

The long-term multicenter observational study of dabigatran treatment in patients with atrial fibrillation (RELY-ABLE) study

Background— During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results— Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE–eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69–1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04–1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80–1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions— During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00808067.

Time to re-appraise the role of alpha-1 adrenoceptor antagonists in the management of hypertension?

The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in uncontrolled hypertension when used in combination with all other major classes of antihypertensive drug and there is increasing evidence suggesting that they have modest but significant beneficial effects on lipid and glucose metabolism. The availability of extended-release formulations has contributed to an excellent tolerability profile. New data from an observational analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that doxazosin gastrointestinal therapeutic system (GITS) used as a third-line antihypertensive agent lowered blood pressure and caused modest reductions in plasma lipids. Furthermore, use of doxazosin in ASCOT was not associated with an increased risk of heart failure, in contrast to the earlier finding of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Overall, currently available data support the use of alpha-blockers as safe, well tolerated and effective add-on antihypertensive drugs, which have additional favourable metabolic effects.

Cohort Profile: The electricity generating authority of Thailand study

During the past 30–40 years, there has been a tremendous increase in the prevalence of cardiovascular disease (CVD), especially in developing countries. The change from an agricultural to an industrial society, and the introduction of new technology, make people less likely to engage in physical activity and more likely to adopt a sedentary lifestyle. Modern medicine has markedly reduced the mortality from infectious disease and has improved human longevity, consequently leading to more deaths from chronic diseases, particularly cancer and CVD. Thailand, a mediumsized middle-income country, is one of those nations that is encountering this epidemiological transition and is anticipated to experience much greater increases in CVD compared with Western countries over the next 20 years. Observational studies in Western populations suggest that the well-established risk factors for CVD (obesity, diabetes mellitus, elevated blood pressure, dyslipidemia and cigarette smoking) account for most of the attributable risk for CVD. But the manifestations of CVD and prevalence of its risk factors are often different among Western and Asian populations. For instance, stroke is much more common among many Asian populations compared with the USA or European Union. Most CVD events are potentially preventable through modification of risk factors. To prioritize the preventive measures for maximum benefit, and influence change, a clear understanding of the attribution of risk factors in the local environment is needed. Consequently, following the model of the Framingham study, the first cohort study of chronic disease in Thailand was set up by a group of cardiologists at Ramathibodi Hospital, Bangkok, in 1985. Their basic aim was to examine the effects of cardiovascular risk factors, as identified by Framingham and other studies, on health in the Thai population, specifically to see if the same risk factors worked in the same way as elsewhere. Due to issues with contacting participants in a general population setting within Thailand, it was decided to site this study within an occupational workforce. Initial funding was provided by Mahidol University, the Thai Heart Association and the Electricity Generating Authority of Thailand (EGAT) corporation. Later, the National Research Council, Thailand Research Fund and Praman Chansue Foundation became major funders.

Long-term effects of socioeconomic status on incident hypertension and progression of blood pressure

Objective: Few data have linked socioeconomic status (SES) to incident hypertension, and little information on the relationship between SES and hypertension are available from developing countries. We thus investigated the long-term effects of SES on incident hypertension and changes in blood pressure in Thailand. Methods: In 1985, baseline data were collected from 3499 participants in the Electricity Generating Authority of Thailand study. Participants were re-examined in 1997, 2002 and 2007. Logistic regression models, Cox-proportional hazard models and time-dependent covariates were used to calculate the relationship between SES and prevalent hypertension in 1985, incident hypertension in 1997 and 2007, respectively. Results: The prevalence of hypertension was 20% and the level of income, but not education, was inversely related to prevalent hypertension. Adjusting for several risk factors, compared to those who had tertiary education, participants who had primary education had 30% increased risk of incident hypertension in 1997 [hazard ratio 1.30, 95% confidence interval (CI) 1.09–1.54] and 20% in 2007 (1.20, 1.05–1.37); both P for trend was less than 0.01. Participants who had higher education also had substantially lower increments in SBP and DBP across 22 years (P < 0.0001 for SBP and P = 0.015 for DBP). Level of income was similarly negatively related to the progression of SBP, with a 3.6 mmHg difference between the highest income group and the lowest (P < 0.0001). Conclusion: Hypertensive counseling and surveillance should be emphasized within socioeconomically disadvantaged populations.

Associations Between Serum Lipids and Causes of Mortality in a Cohort of 3499 Urban Thais: The Electricity Generating Authority of Thailand (EGAT) Study

The association between serum lipids and mortality has not previously been established in Thailand. Baseline data from the Electricity Generating Authority of Thailand (EGAT) cohort study, plus a resurvey of the cohort 15 years later were analyzed. Participants were employees of EGAT: 2702 men and 797 women. Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were taken as predictive variables; age, sex, hypertension, diabetes, cigarette smoking, alcohol drinking, and body mass index were taken as confounders. Dependent variables were all-causes and specific causes of mortality over 17 years of follow-up. The major cause of death among men was cardiovascular disease (CVD); among women, it was cancer. Relative risks (RR) for specific causes of death, for a mmol/L increase in each lipid, were estimated after adjustment for confounding factors using Cox proportional hazards regression. TC and LDL-C were negatively associated with liver cirrhosis mortality, although it was likely that the low cholesterol concentration was a consequence of the disease. HDL-C was negatively associated with CVD mortality (RR = 0.59; 95% confidence interval [CI], 0.39-0.93), coronary heart disease (CHD) mortality (RR = 0.36; 95% CI, 0.17-0.75) and all cause-mortality (RR = 0.68; 95% CI, 0.54-0.87). TG was not associated with mortality. HDL-C is an important risk factor for CVD in middle-class urban Thais. Health promotion programs to improve lipid profiles, such as effective exercise campaigns and dietary advice, are required to increase HDL-C and to help prevent CVD and premature death in Thailand.

Efficacy and Safety of Dabigatran Versus Warfarin in Patients with Atrial Fibrillation : Analysis in Asian Population in RE-LY Trial

Efficacy and Safety of Dabigatran Versus Warfarin in Patients with Atrial Fibrillation : Analysis in Asian Population in RE-LY Trial